Progressive multifocal leukoencephalopathy (PML) and AIDS encephalopathy are virally induced neurological diseases which occur almost exclusively in the setting of a dysimmune state. We have investigated the molecular pathogenesis of these diseases by developing laboratory assays that examine the human polyomavirus, JCV as the cause of PML, and the Human Immunodeficiency Virus, HIV- 1, in AIDS. We have found that human fetal glial and adult B cells have common DNA proteins binding factors which recognize the regulatory sequences of JCV DNA Furthermore, we have also demonstrated the presence of JCV in B cells found in demyelinated white matter from cases of PML. Using PCR technology, the presence of JCV DNA in peripheral blood lymphocytes of PML patients was noted. These data suggest that the B cell may act as a hematogenous vector for JCV infection of the nervous system. The identification of the JCV genome DNA in peripheral blood lymphocytes has also been made in several AIDS patients who do not have PML suggesting that JCV may circulate in the blood prior to the time of clinical neurological disease. These individuals are considered at high risk of developing PML. The role of astroglial cells in the brain in the pathogenesis of AIDS encephalopathy has also been studied. Astrocytes from human fetal brain rapidly transcribe the HIV- 1 genome when it is transfected into cells in culture.A short period of productive infection is followed by a stage of persistent viral infection. The cells will re-enter a productive phase of infection in the presence of T cells or the cytokines tumor necrosis factor-alpha and interleukin l beta. HIV-I infected astrocytes can also be identified in the brain tissue of pediatric AIDS patients. Human fetal astrocytes and Schwann cells have also been shown to be susceptible to other neurotropic human viruses such as varicella-zoster virus which causes shingles. These cell types may also serve as sites of viral latency during the many years between initial infection and demonstration of neuronal infection.